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991.
Chao Wei Wei Zhang Qiong Zhou Chao Zhao Ying Du Qi Yan Zhuyi Li Jianting Miao 《Neurochemical research》2016,41(8):1924-1938
Increasing evidence has shown that specificity protein 1 (Sp1) is abnormally increased in the brains of subjects with Alzheimer’s disease (AD) and transgenic AD models. However, whether the Sp1 activation plays a critical role in the AD pathogenesis and selective inhibition of Sp1 activation may have a disease-modifying effect on the AD-like phenotypes remain elusive. In this study, we reported that Sp1 mRNA and protein expression were markedly increased in the brain of APPswe/PS1dE9 transgenic mice, whereas chronic administration of mithramycin A (MTM), a selective Sp1 inhibitor, potently inhibited Sp1 activation in the APPswe/PS1dE9 mice down to the levels of wild-type mice. Specifically, we found that MTM treatment resulted in a significant improvement of learning and memory deficits, a dramatic reduction in cerebral Aβ levels and plaque burden, a profound reduction in tau hyperphosphorylation, and a marked increase in synaptic marker in the APPswe/PS1dE9 mice. In addition, MTM treatment was powerfully effective in inhibiting amyloid precursor protein (APP) processing via suppressing APP, beta-site APP cleaving enzyme 1 (BACE1), and presenilin-1 (PS1) mRNA and protein expression to preclude Aβ production in the APPswe/PS1dE9 mice. Furthermore, MTM treatment strongly inhibited phosphorylated CDK5 and GSK3β signal pathways to reduce tau hyperphosphorylation in the APPswe/PS1dE9 mice. Collectively, our findings provide evidence that Sp1 activation may contribute to the AD pathogenesis and may serve as a novel therapeutic target in the treatment of AD. The present study highlights that selective Sp1 inhibitors may be considered as disease-modifying therapeutic agents for AD. 相似文献
992.
Johannes W. S. A. Osterloh Arjan C. Videler Gina M. P. Rossi Sebastiaan P. J. van Alphen 《Tijdschrift voor gerontologie en geriatrie》2018,49(5):210-212
Behavioural counselling by nurses can enhance quality of life in elderly with a personality disorder. Although nurses have a crucial role in day-to-day treatment, there is a lack of evidence-based approaches. Based on the cognitive therapy, the treatment protocol Cognitive Model for Behavioural Interventions (CoMBI) provides an alternative nursing approach for personality disorders. 相似文献
993.
994.
Iigo Zuberogoitia Jos Enrique Martínez Jos Antonio Gonzlez‐Oreja Juan Manuel Prez de Ana Jabi Zabala 《Ibis》2019,161(4):878-889
Two hypotheses have been proposed to link population regulation to density‐dependent changes in demographical parameters: the habitat heterogeneity hypothesis (HHH) states that, as population density rises, an increasing proportion of individuals are forced to occupy low‐quality territories, which provokes a decline in average per‐capita survival and/or productivity although some individuals show no decline in fecundity; and the individual adjustment hypothesis (IAH), which suggests that increased densities lead to reductions in survival and/or fecundity by enhancing agonistic interactions, which affect all individuals to a similar extent. However, density‐dependent effects can be affected by density‐independent factors (DIF), such as weather. We test the effects of density dependence on annual reproductive success in Griffon Vultures Gyps fulvus at four spatial scales, nest‐site, cliff, colony and metacolony, in northern Spain from 2008 to 2015. Our results showed most support for the HHH at all scales. At the colony and cliff scale, IAH and DIF had similar importance, whereas there was little evidence of IAH at the metacolony and the nest scale. The best protected eyries (caves, potholes and sheltered ledges) produced the most fledglings and were used preferentially, whereas low‐quality eyries (exposed ledges or open crevices) were used only when the number of breeders increased. The significant interaction between breeding failure and density found for the more exposed eyries suggests that at higher densities, breeding pairs are forced to use poorer nesting areas, and the negative effect of density at the cliff scale could be due to the combined effect of a higher proportion of pairs using low‐quality eyries and the negative effect of rainfall. 相似文献
995.
996.
Dalia Rokhsana David M. Dooley Robert K. Szilagyi 《Journal of biological inorganic chemistry》2008,13(3):371-383
A systematic in silico approach has been employed to generate sound, experimentally validated active-site models for galactose oxidase (GO) using a hybrid density functional, B(38HF)P86. GO displays three distinct oxidation states: oxidized [Cu(II)-Y*]; semireduced [Cu(II)-Y]; and reduced [Cu(I)-Y]. Only the [Cu(II)-Y*] and the [Cu(I)-Y] states are assumed to be involved in the catalytic cycle, but their structures have not yet been determined. We have developed several models (1-7) for the [Cu(II)-Y*] state that were evaluated by comparison of our computational results with experimental data. An extended model system (6) that includes solvent molecules and second coordination sphere residues (R330, Y405, and W290) is essential to obtain an experimentally correct electronic structure of the active site. The optimized structure of 6 resulted in a five-coordinate Cu site with a protein radical centered on the Tyr-Cys cofactor. We further validated our converged model with the largest model (7) that included additional outer-sphere residues (Q406, H334, Y329, G513, and T580) and water molecules. Adding these residues did not affect significantly the active site's electronic and geometric structures. Using both 6 and 7, we explored the redox dependence of the active-site structure. We obtained four- and three-coordinate Cu sites for [Cu(II)-Y] and [Cu(I)-Y] states, respectively, that corroborate well with the experimental data. The relative energies of these states were validated by a comparison with experimental redox potentials. Collectively, our computational GO models well reproduce the physicochemical characteristics of the individual states, including their redox behaviors. 相似文献
997.
Vanesa M. Fernández Andrés Arenas Walter M. Farina 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2009,195(8):759-768
Honeybees of different ages and reproductive castes cohabit in the hive where they are exposed to many odors that might affect
associative learning. Our aim was to analyze the role of odors pre-exposed as volatiles on appetitive learning in honeybees
of different ages and search for their long-term effect both under natural and laboratory conditions. By evaluating memory
acquisition and retention through a differential proboscis extension response conditioning, we found that hive-exposed odors
offered as a reinforced conditioned stimulus during training promoted a learning-reduced effect [latent inhibition (LI)].
On the other hand, no effect was found when the non-reinforced conditioned stimulus was pre-exposed. The LI effect varied
with the odor identity. However, only slight differences were found with the age of the bees. Exposure-conditioning intervals
longer than 24 h did not show an LI effect unless the odor concentration was increased or exposure was prolonged. Our results
show that pre-exposed volatiles could either reduce learning performance, if this odor is later associated with food, or be
irrelevant in the case that alternative scented resources circulate within the colony. The differential effects found according
to the olfactory exposure characteristics could strongly influence the propagation of chemosensory information within the
hive. 相似文献
998.
Miller LM Wang Q Telivala TP Smith RJ Lanzirotti A Miklossy J 《Journal of structural biology》2006,155(1):30-37
Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (Abeta). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 microm was achieved. FTIRM results showed that the amyloid plaques have elevated beta-sheet content, as demonstrated by a strong amide I absorbance at 1625cm(-1). Using SXRF microprobe, we find that AD tissue also contains "hot spots" of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The "hot spots" of accumulated Zn and Cu were co-localized with beta-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated beta-sheet content in Abeta plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD. 相似文献
999.
1000.
Judith Zhi-Yie Tan Stephen M Schlicht Gerard J Powell David Thomas John L Slavin Peter J Smith Peter FM Choong 《International Seminars in Surgical Oncology : ISSO》2006,3(1):38